The goal of this research is to further elucidate the physiological properties of chemical synapses between nerve cells. In particular, this project considers the entry of calcium (Ca) ions into presynaptic nerve terminals and the ability of Ca ions within nerve terminals to trigger transmitter secretion. Experiments will be performed upon squid 'giant' presynaptic terminals, one of the few nerve terminals large enough to permit direct, electrical measurements of Ca entry and accumulation. This project considers several aspects of the role of Ca in presynaptic function. Entry of Ca ions into presynaptic terminals will be assessed by measuring Ca currents with the 3-microelectrode voltage clamp method. The hypothesis that the neuropeptide enkephalin decreases synaptic transmission by decreasing entry of Ca ions into presynaptic terminals will be tested by examining the effect of enkephalin upon voltage-gated Ca currents. The ability of Ca ions within presynaptic terminals to trigger transmitter release will be examined by measuring the relationship between external Ca concentration, Ca entry and transmitter release. These experiments will also use Ca-sensitive microelectrodes to ask whether presynaptic neurotoxins trigger transmitter release by increasing the concentration of Ca ions within nerve terminals. Consideration of these specific roles of Ca ions in the function of presynaptic terminals will help define the physiological processes underlying synaptic transmission, and may ultimately clarify the action of numerous neurological disorders which result from abnormal synaptic function.